The purpose of this proposal is to resolve a long-standing controversy concerning the efficacy of immunotherapy in the management of allergic asthma. A multicenter clinical investigative study has been organized to accomplish this goal. The research design of the immunotherapy program will be a randomized, multicenter, double blind controlled protocol comparing the effectiveness of high dose allergen (i.e., house dust mite) immunotherapy with color matched histamine placebo in comparable groups of patients with allergic asthma. At the conclusion of the study, intergroup differences of clinical response, pulmonary function changes, bronchial hyperreactivity, skin test titrations, serologic changes and dose response thresholds of early and late phase bronchoprovocation tests will be analyzed by a multi-variate statistical method. The protocol is designed to have a prescreening, baseline ("run-in"), rush immunotherapy and long term maintenance immunotherapy periods of study for a total period of 36 months. Throughout this time, dust samples from each patient's home will be assayed for total number of mites, live/dead ratios and total mite allergenic load. All diagnostic and treatment materials will be supplied by one extract manufacturer. The quality of the extracts will be pre-checked by the manufacturer but will also be assured by quality control tests (RAST inhibition, skin potency, CRIE) at the project principal investigator's parent institution. The dust sampling data will also be included in the multi-variate analysis at the conclusion of the study. A group of distinguished clinical investigators have agreed to participate in the study. Clinical coordination, immunologic core studies and biostatistical supervision will be performed at the parent institution of the project principal investigator.